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The scenario of systemic therapy for prostate cancer is rapidly evolving, with new drugs and new treatment options. To update the background knowledge of shared uro-oncologic practice, we reviewed current statements and landmarks in systemic therapy. A number of new agents are under investigation in non-metastatic and metastatic disease. Similarly, new target imaging technologies are under development to improve the detection rate of true non-metastatic and true metastatic patient. Five new drugs have shown to be effective on progression-free and overall survival in metastatìc prostate cancer. However, the optimal sequencing of these treatments requires further investigation. The tolerability and side effects of the new drugs are also crucial issues to be discussed, as well as their activity against the disease. The uro-oncologic team has to stay updated about new medical therapies in order to be confident in debating with other professionals involved in prostate cancer decision making. Different points of view and nuances should be shared during multidisciplinary group discussions to achieve a balanced decision in disease management.

Francesco Perri,1 Salvatore Pisconti,1 Manuel Conson,2,3 Roberto Pacelli,2,3 Giuseppina Della Vittoria Scarpati,2 Antonio Gnoni,1 Carmine D’Aniello,1 Carla Cavaliere,1 Antonella Licchetta,1 Laura Cella,2,3 Mario Giuliano,4,5 Concetta Schiavone,7 Sara Falivene,7 Giuseppe Di Lorenzo,4 Carlo Buonerba,6 Vincenzo Ravo,7 Paolo Muto7 1Medical Oncology Unit, POC S Annunziata, Taranto, 2Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, 3Institute of Biostructures and Bioimaging, National Council of Research, Naples, 4Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 5Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA; 6Division of Oncology, Centro di riferimento Oncologico di Basilicata, IRCCS Rionero in Vulture, Potenza, 7Department of Radiotherapy, Istituto Nazionale per la Cura dei Tumori-Fondazione G. Pascale. IRCCS di Napoli, Naples, Italy Background: The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. Methods: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44–60) Gy was delivered to the tumor bed by 6–20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter.Results: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. Conclusion: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma. Keywords: thymoma, adjuvant treatment, three-dimensional conformal radiotherapy, local control, toxicity&nbsp

Multiple dermal cylindromas and membranous basal cell adenoma of parotid gland in a 67-year-old woman with Brooke-Spiegler syndrome (BSS) were examined by fine-needle cytology. Histology, immunochemistry, and CYLD germline mutation testing were also performed. Cytomorphology and immunochemistry of the two lesions showed basaloid neoplasms, remarkably similar, composed by proliferating epithelial cells of basal type accompanied by a smaller proportion of myoepithelial cells. CYLD gene showed a novel germline splice acceptor site mutation (c.2042-1G>C) with skipping of the entire exon 15. The occurrence of analogous tumors, dermal cylindromas, and membranous basal cell adenoma of the parotid gland, in the same patient may result from the action of a single gene on ontogenetically similar stem cells. Therefore, patients with BSS should be offered a genetic counselling for an early and correct diagnosis.

Introduction: Total skin electron beam (TSEB) therapy represents a valid treatment option in the management of patients with cutaneous T-Cell lymphoma (CTCL) with diffuse skin involvement. While the efficacy of TSEB for palliative treatment is well established, its inclusion as a debulking strategy before reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been only recently reported. Due to the lack of hematopoietic toxicity, TSEB may also be effectively administered in patients relapsing after allo-HSCT. With this study we aimed to retrospectively investigate the use of TSEB among patients who underwent to allo-HSCT in our Center for advanced CTCL. Patients & Methods: As of July 2019, 45 CTCL patients (26 M and 19 F, median age 54 years, range 19-66) all having stage IIB to IV refractory Mycosis Fungoides (MF, n=33) or Sézary Syndrome (SS, n=12) underwent allo-HSCT from HLA-identical sibling (n=18), unrelated donors (n=23) or haploidentical related donors (n=4). Median time from diagnosis to HSCT was 46 months and median number of previous treatment lines was 6. Source of stem cells was peripheral blood in 40 patients, bone marrow in 4 patients and cord blood in 1 patient. Conditioning regimens included FC/TBI200, pentostatin/TBI200, fludarabine/melphalan and TT/CTX/Fluda/TBI200. Outcomes at 5-years were: OS 51% (33%-66%), DFS 40% (20%-50%), NRM 15% (4%-27%) and relapse incidence 48% (32%-65%). Clinical charts of the whole series of patients were extensively reviewed to collect information on the use of TSEB from diagnosis to the last follow up date. Results: Overall 21 patients of the series received TSEB with dose fractionation of 2 Gy in 2 days administered with the Stanford Technique as part of their treatment strategy. In six cases it was included among the lines of treatment administered over the disease course preceding transplant referral, with a total dose of 36 Gy in all of them. In 13 patients TSEB was part of the debulking strategy for patients with chemorefractory disease just prior to allo-HSCT with a median total dose of 24 Gy (range 10.8- 36). In 4 patients TSEB was administered after transplantation: as a salvage treatment for skin relapse during early post tranplant intense immunosuppression phase in 3 cases (12, 36, 21.6 Gy respectively) and as palliative treatment for disease progression in one case (36 Gy). Among patients who received TSEB as a bridge to transplant strategy, CR was achieved in 5 cases: at the last follow up visit (median time from transplantation 23 months, range 6-80) 4 were alive with persistent CR, whereas 1 patient who experienced graft failure died from disease progression 31 months after transplantation. Partial remission (PR) was documented in 7 (very good in 2): at the last follow up visit (median time from transplantation 14 months, range 6-52) 2 patients were alive in CR and 5 died: 3 from disease progression, 1 from GVHD and 1 from myocardial infarction 42 months after transplantion. In 1 patient, who only showed minimal response to TSEB therapy, death from disease progression occurred 9 months after an autologous-allogeneic tandem transplant strategy. All the 3 patients receiving TSEB after allo-HSCT for early relapse achieved a new and durable CR maintained at the last follow up date (42, 21 and 10 months after transplant respectively), suggesting the occurrence of a durable graft-versus-lymphoma effect following TSEB. As far as safety is concerned, only grade 1 skin toxicity (erythematous reactions) was observed in a minority of patients, while no case of haematological toxicity was documented. Conclusions: Our experience confirmed TSEB as a particularly safe and potentially effective treatment strategy in CTCL patients, both to induce remission prior to allo-HSCT and to rescue early post transplant relapse occurring before immunosuppression withdrawal. Disclosures No relevant conflicts of interest to declare.

Multiple dermal cylindromas and membranous basal cell adenoma of parotid gland in a 67-year-old woman with Brooke-Spiegler syndrome (BSS) were examined by fine-needle cytology. Histology, immunochemistry, and CYLD germline mutation testing were also performed. Cytomorphology and immunochemistry of the two lesions showed basaloid neoplasms, remarkably similar, composed by proliferating epithelial cells of basal type accompanied by a smaller proportion of myoepithelial cells. CYLD gene showed a novel germline splice acceptor site mutation (c.2042-1GC) with skipping of the entire exon 15. The occurrence of analogous tumors, dermal cylindromas, and membranous basal cell adenoma of the parotid gland, in the same patient may result from the action of a single gene on ontogenetically similar stem cells. Therefore, patients with BSS should be offered a genetic counselling for an early and correct diagnosis.

Nasopharyngeal carcinoma is rare in western countries, accounting for less than 1% of all malignancies. Despite prognosis is satisfactory for newly diagnosed, non-metastatic disease, management of recurrent disease is challenging, with a survival expectancy of approximately 6 mo with the use of chemotherapy as the sole salvage treatment. We report a case of recurrent nasopharyngeal carcinoma treated with a combination of chemotherapy, radiotherapy and surgery in the context of a multidisciplinary approach. A durable complete response was achieved.

AIM: To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma (NPC). METHODS: We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy (CCRT) (22/40 patients) or CCRT alone (18/40) from March 2006 to March 2012. Patients underwent fiberoscopy with biopsy of the primitive tumor, and computed tomography scan of head, neck, chest and abdomen with and without contrast. Cisplatin was used both as induction and as concomitant chemotherapy, while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions (total dose, 70 Gy). The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly. This retrospective analysis was approved by the review boards of the participating institutions. Patients gave their consent to treatment and to anonymous analysis of clinical data. RESULTS: Thirty-three patients were males and 7 were females. Median follow-up time was 58 mo (range, 1-92 mo). In the sub-group of twenty patients with a follow-up time longer than 36 mo, the 3-year survival and disease free survival rates were 85% and 75%, respectively. Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%. Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients. Grade 2 mucositis was seen in 29 patients, while grade 2 xerostomia was seen in 30 patients. Overall toxicity was manageable and it did not cause any significant treatment delay. In the whole sample population, long term toxicity included grade 2 xerostomia in 22 patients, grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients. CONCLUSION: Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC. The role of adjuvant chemotherapy remains to be defined.

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50–60 Gy in 2 Gy daily fractions. New metastases appear in 22–73% of the cases after whole brain radiotherapy, but the percentage of re-irradiated patients is 3–10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status >70, age In general, the incidence of an “in-field” recurrence of spinal metastasis varies from 2.5–11% of cases and can occur 2–40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An α/β ratio of 1.9–3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment.

Background and purpose To report recommendations given in the Multinational Association of Supportive Care in Cancer (MASCC) International Consensus Conference regarding the use of antiemetics in radiotherapy. Patients and methods A steering committee under MASCC auspice chose panel participants for the guidelines development process on prevention of chemotherapy- and radiotherapy-induced emesis (RIE). Pertinent information from published literature as of March 2004 was reviewed for the guideline process. Both the MASCC level of scientific confidence and level of consensus, and the American Society of Clinical Oncology (ASCO) type of evidence and grade for recommendation were adopted. Results Total body irradiation is classified at high risk, upper abdomen at moderate, lower thorax, pelvis, cranium (radiosurgery) and craniospinal at low, head and neck, extremities, cranium and breast at minimal risk. The recommendations for the use of antiemetics in radiotherapy are as follows: prophylaxis with a 5-HT3 antagonist in patients at high and moderate risk levels of RIE (±dexamethasone in the former group), prophylaxis or rescue with a 5-HT3 antagonist in the low risk group, and rescue with dopamine or a 5-HT3 receptor antagonist in minimal risk level. Conclusions These recommendations represent a valid tool for prophylaxis and treatment of RIE in clinical practice.